Lungs:

Diseases of Vascular Origin

Diseases of Vascular Origin

Pulmonary Embolism and Infarction

Pulmonary Hypertension
Diffuse Pulmonary Hemorrhage Syndromes
Goodpasture Syndrome
Idiopathic Pulmonary Hemosiderosis
Polyangiitis With Granulomatosis
Pulmonary Infections
 Pulmonary Embolism and Infarction

• an important cause of morbidity and mortality, particularly in patients who

are bedridden
• but also in a wide range of conditions that are associated with hypercoagulability
• Blood clots that occlude the large pulmonary arteries are almost always embolic in
origin.
• The usual source—thrombi in the deep veins of the leg (>95% of cases)
 Pulmonary Embolism and Infarction

• Pathogenesis.
• Pulmonary embolism usually occurs in patients with a predisposing condition that
produces an increased tendency to clot (thrombophilia)
• Patients often have cardiac disease or cancer
• have been immobilized for several days or weeks
• hip fractures are at particularly high risk
• Hypercoagulable states:
• Primary: (e.g., factor V Leiden, prothrombin mutations, and antiphospholipid syndrome)
• Secondary: (e.g., obesity, recent surgery, cancer, oral contraceptive use, pregnancy)
 Pulmonary Embolism and Infarction

• Emboli have two deleterious pathophysiologic consequences:

• respiratory compromisedue to the nonperfused, although ventilated, segment
• hemodynamic compromise due to increased resistance to pulmonary blood flow
caused by the embolic obstruction. Sudden death often ensues, largely as a result of
the blockage of blood flow through the lungs. Death may also be caused by acute
right-sided heart failure (acute cor pulmonale).
 Pulmonary Embolism and Infarction

ECG: Electromechanical Dissociation, got rhythm but no pulses

Deep vein Thrombosis: Duplex Ultrasound
Embolism: Angiogram
Chest X-ray: normal or show lung infarc; 12-36 hrs later: show wedge-shaped infiltrate
 Clinical Course: Pulmonary Embolism and
Infarction
• A large pulmonary embolus is one of the few causes of virtually instantaneous death
• During cardiopulmonary resuscitation in such instances, the patient frequently is said to
have electromechanical dissociation, in which the electrocardiogram has a rhythm but no pulses
are palpated because no blood is entering the pulmonary arterial circulation
• If the patient survives after a sizable pulmonary embolus, however, the clinical syndrome may mimic
myocardial infarction, with severe chest pain, dyspnea, and shock
• Small emboli are silent or induce only transient chest pain and cough.
• Pulmonary infarcts manifest as dyspnea, tachypnea, fever, chest pain, cough, and hemoptysis
• An overlying fibrinous pleuritis may produce a pleural friction rub.
 Clinical Course: Pulmonary Embolism and
Infarction
• Findings on chest radiograph are variable and can be normal or disclose a pulmonary infarct, usually 12 to 36
hours after it has occurred, as a wedge-shaped infiltrate
• The diagnosis of pulmonary embolism is usually made with spiral computed tomographic angiography
• Deep vein thrombosis can be diagnosed with duplex ultrasonography
• Prevention of pulmonary embolism is a major clinical challenge for which there is no easy solution
• Prophylactic therapy includes early ambulation in postoperative and postpartum patients, elastic stockings
and graduated compression stockings for bedridden patients, and anticoagulation in high-risk individuals
• Treatment of pulmonary embolism includes anticoagulation and supportive measures; thrombolysis may
have some benefit in those with severe complications (e.g., shock), but carries a high risk of bleeding. Those
at risk of recurrent pulmonary embolism in whom anticoagulation is contraindicated may be fitted with an
inferior vena cava filter (an “umbrella”) that catches clots before they reach the lungs.
 Pulmonary Hypertension

• defined as a mean pulmonary artery pressure greater than or equal to 25 mm Hg at rest

• Based on underlying mechanisms, the World Health Organization has classified pulmonary
hypertension into five groups:
• (1) pulmonary arterial hypertension, a diverse collection of disorders that all primarily impact small
pulmonary muscular arteries;
• (2) pulmonary hypertension secondary to left-heart failure;
• (3) pulmonary hypertension stemming from lung parenchymal disease or hypoxemia;
• (4) chronic thromboembolic pulmonary hypertension
• (5) pulmonary hypertension of multifactorial basis.
 Pathogenesis: Pulmonary Hypertension

• most frequently associated with structural cardiopulmonary conditions that increase pulmonary blood flow, pulmonary vascular resistance,
or left heart resistance to blood flow.
• Chronic obstructive or interstitial lung diseases (group 3).
• obliterate alveolar capillaries, increasing pulmonary resistance to blood flow and, secondarily, pulmonary blood pressure.
• Antecedent congenital or acquired heart disease (group 2)
• Mitral stenosis, for example, causes an increase in left atrial pressure and pulmonary venous pressure that is eventually transmitted to the arterial side of the
pulmonary vasculature, leading to hypertension.
• Recurrent thromboemboli (group 4)
• by reducing the functional cross-sectional area of the pulmonary vascular bed, which in turn leads to an increase in pulmonary vascular resistance.
• Autoimmune diseases (group 1)
• most notably systemic sclerosis involve the pulmonary vasculature and/or the interstitium, leading to increased vascular resistance and pulmonary hypertension.
• Obstructive sleep apnea (also group 3)
• common disorder that is associated with obesity and hypoxemia. It is now recognized to be a significant contributor to the development of pulmonary hypertension
and cor pulmonale.
• Uncommonly, pulmonary hypertension is
encountered in patients in whom all known causes
are excluded; this is referred to as idiopathic
pulmonary arterial hypertension.
• up to 80% of “idiopathic” pulmonary hypertension has
a genetic basis, sometimes being inherited in familes
as an autosomal dominant trait.
• The first mutation to be discovered in familial
pulmonary arterial hypertension was in the bone
morphogenetic protein receptor type 2 (BMPR2)
• BMPR2 is a cell surface protein belonging to the
TGF-β receptor superfamily, which binds a variety
of cytokines, including TGF-β, bone morphogenetic
protein (BMP), activin, and inhibin
• BMP-BMPR2 signaling is now known to be
important for embryogenesis, apoptosis, and cell
proliferation and differentiation. Details remain to
be worked out, but it appears that
haploinsufficiency for BMPR2 leads to dysfunction
and proliferation of endothelial cells and vascular
smooth muscle cells.
 Diffuse Pulmonary
Hemorrhage Syndromes
 Diffuse Pulmonary Hemorrhage Syndromes

• a dramatic complication of some interstitial lung disorders.

• (1) Goodpasture syndrome

• (2) idiopathic pulmonary hemosiderosis
• (3) vasculitis-associated hemorrhage, which is found in conditions such as
hypersensitivity angiitis, Wegener granulomatosis, and systemic lupus
erythematosus
 Goodpasture Syndrome

• uncommon autoimmune disease in which kidney and lung injury are caused
by circulating autoantibodies against the noncollagenous domain of the α3
chain of collagen IV
• When only renal disease is caused by this antibody, it is called anti-
glomerular basement membrane disease
• The term Goodpasture syndrome designates the 40% to 60% of patients
who develop pulmonary hemorrhage in addition to renal disease
 Idiopathic Pulmonary Hemosiderosis

• a rare disorder characterized by intermittent, diffuse alveolar hemorrhage. Most cases

occur in young children, although the disease has been reported in adults as well.
• The cause and pathogenesis are unknown
• no anti-basement membrane antibodies are detectable in serum or tissues.
• However, favorable response to long-term immunosuppression with prednisone and/or
azathioprine indicates that an immunologic mechanism could be involved in the pulmonary
capillary damage underlying alveolar bleeding. In addition, long-term follow-up of patients
shows that some of them develop other immune disorders.
 Polyangiitis with Granulomatosis

• Previously called Wegener granulomatosis

• this autoimmune disease most often involves the upper respiratory tract and/or the
lungs
• a transbronchial lung biopsy might provide the only tissue available for diagnosis
• Since the amount of tissue is small, necrosis and granulomatous vasculitis might
not be present
• Rather, the diagnostically important features are capillaritis and scattered, poorly
formed granulomas
Pulmonary Infections
The local defense mechanisms of the lung can be compromised by
many factors, including:

• Loss or suppression of the cough reflex

• result of coma, anesthesia, neuromuscular disorders, drugs, or chest pain
• Injury to the mucociliary apparatus by either impairment of ciliary function or destruction of ciliated epithelium
• due to cigarette smoke, inhalation of hot or corrosive gases, viral diseases, or genetic defects of ciliary function (e.g., the immotile cilia
syndrome)
• Accumulation of secretions in conditions
• cystic fibrosis and bronchial obstruction
• Interference with the phagocytic or bactericidal action of alveolar macrophages
• alcohol, tobacco smoke, anoxia, or oxygen intoxication
• Pulmonary congestion and edema
Lobar Pneumonia
4 stages:
Lung Transplant
 Lung Transplant

• most common indications:

• end-stage emphysema
• idiopathic pulmonary fibrosis
• cystic fibrosis
• idiopathic/familial pulmonary arterial hypertension
 2 MAJOR COMPLICATIONS

• Pulmonary infections
• Rejection
• Acute: weeks - months
• Chronic : 3-5 years
Next session
Some music to wake you up
Tumors
• A variety of benign and malignant tumors may arise in the lung,

• but 90% to 95% are carcinomas,

• about 5% are bronchial carcinoids, and 2% to 5% are mesenchymal and

other miscellaneous neoplasms.
 Risk Factors

• Genetics
• Smoking
• industrial exposures, such as asbestos, arsenic, chromium, uranium, nickel,
vinyl chloride and mustard gas
• Nukes
• Air pollution
• Small cell Ca: small
but terrible
• AdenoCa: Female
non-smoker
 Neuroendocrine Proliferations and Tumors

• Carcinoid Tumors
• low-grade malignant epithelial neoplasms that are subclassified into typical and
atypical carcinoids.
Pleura
• Pathologic involvement of the pleura is, most often, a secondary complication of
some underlying disease
• Secondary infections and pleural adhesions are particularly common findings at
autopsy
• Important primary disorders include:
• (1) primary intrapleural bacterial infections that imply seeding of this space as an isolated
focus in the course of a transient bacteremia
• (2) a primary neoplasm of the pleura: mesothelioma
 Pleural Effusion

• a common manifestation of both primary and secondary pleural diseases, which may be inflammatory or noninflammatory
• Normally, no more than 15 mL of serous, relatively acellular, clear fluid lubricates the pleural surface
• Accumulation of pleural fluid occurs in the following settings:
• Increased hydrostatic pressure, as in congestive heart failure

• Increased vascular permeability, as in pneumonia

• Decreased osmotic pressure, as in nephrotic syndrome

• Increased intrapleural negative pressure, as in atelectasis

• Decreased lymphatic drainage, as in mediastinal carcinomatosis

 Empyema

• is characterized by loculated, yellow-green, creamy pus composed of

masses of neutrophils admixed with other leukocytes
• Although empyema may accumulate in large volumes (up to 500 to
1000 mL), usually the volume is small, and the pus becomes localized.
• may resolve, but more often the exudate organizes into dense, tough
fibrous adhesions that frequently obliterate the pleural space or envelop the
lungs; either can seriously restrict pulmonary expansion.
 Hydrothorax

• Noninflammatory collections of serous fluid within the pleural cavities

• fluid is clear and straw colored
• may be unilateral or bilateral
• The most common cause of hydrothorax is cardiac failure, and for this reason it is
usually accompanied by pulmonary congestion and edema
• Transudates may also collect in any other systemic disease associated with
generalized edema and are therefore found in renal failure and cirrhosis of the liver.
• Hemothorax:
• The escape of blood into the pleural cavity
• It is almost invariably a fatal complication of a ruptured aortic aneurysm or vascular trauma or it may
occur postoperatively.
• Chylothorax:
• accumulation of milky fluid, usually of lymphatic origin, in the pleural cavity. Chyle is milky white
because it contains finely emulsified fats
• most often caused by thoracic duct trauma or obstruction that secondarily causes rupture of major
lymphatic ducts
• typically caused by malignancies that obstruct the major lymphatic ducts
 Pneumothorax

• refers to air or gas in the pleural cavities and is most commonly associated with emphysema,
asthma, and tuberculosis
• It may be spontaneous, traumatic, or therapeutic
• Spontaneous pneumothorax may complicate any form of pulmonary disease that causes rupture
of an alveolus. An abscess cavity that communicates either directly with the pleural space or
with the lung interstitial tissue may also lead to the escape of air. In the latter circumstance the
air may dissect through the lung substance or back through the mediastinum (interstitial
emphysema), eventually entering the pleural cavity
• Traumatic pneumothorax is usually caused by some perforating injury to the chest wall, but
sometimes the trauma pierces the lung and thus provides two avenues for the accumulation of
air within the pleural spaces